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Aberrantly methylated-differentially expressed genes and pathways in Epstein-Barr virus-associated gastric cancer.

Epstein-Barr 病毒相关胃癌中异常甲基化差异表达的基因和通路。

  • 影响因子:1.71
  • DOI:10.2217/fon-2019-0649
  • 作者列表:"Jing JJ","Li H","Wang ZY","Zhou H","Sun LP","Yuan Y
  • 发表时间:2020-01-28
Abstract

:Aim: To identify the methylated-differentially expressed genes (MDEGs) that may serve as diagnostic markers and therapeutic targets in Epstein-Barr virus-associated gastric cancer (EBVaGC) and to explore the methylation-based pathways for elucidating biological mechanisms of EBVaGC. Materials & methods: Gene expression and methylation profiles were downloaded from GEO database. MDEGs were identified by GEO2R. Pathway enrichment analyses were conducted based on DAVID database. Hub genes were identified by Cytoscape, which were further verified by The Cancer Genome Atlas database. Results: A total of 367 hypermethylated, lowly expressed genes were enriched in specific patterns of cell differentiation. 31 hypomethylated, highly expressed genes demonstrated enrichment in regulation of immune system process. After validation using The Cancer Genome Atlas database, seven genes were confirmed to be significantly different hub genes in EBVaGC. Conclusion: EBVaGC-specific MDEGs and pathways can be served as potential biomarkers for precise diagnosis and treatment of EBVaGC and provide novel insights into the mechanisms involved.

摘要

目的:鉴定可作为EBVaGC诊断标志物和治疗靶点的甲基化差异表达基因(MDEGs),探讨其甲基化途径,阐明EBVaGC的生物学机制。材料与方法:从GEO数据库下载基因表达谱和甲基化谱。利用GEO2R鉴定MDEGs,并基于DAVID数据库进行路径富集分析。Hub基因由细胞图谱鉴定,并由肿瘤基因组图谱数据库进一步验证。结果:共有367个高甲基化、低表达的基因在特定的细胞分化模式中富集。31个低甲基化、高表达的基因在免疫系统过程的调控中表现出丰富性。在使用癌症基因组图谱数据库进行验证后,7个基因被证实是EBVaGC中显著不同的hub基因。结论:EBVaGC特异性MDEGs和通路可作为EBVaGC精确诊断和治疗的潜在生物标志物,为EBVaGC的发病机制提供新的线索。

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DOI:10.1002/mc.23158
作者列表:["Xie W","Chen C","Han Z","Huang J","Liu X","Chen H","Zhang T","Chen S","Chen C","Lu M","Shen X","Xue X"]

METHODS::Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.

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影响因子:1.71
发表时间:2020-01-28
DOI:10.2217/fon-2019-0649
作者列表:["Jing JJ","Li H","Wang ZY","Zhou H","Sun LP","Yuan Y"]

METHODS::Aim: To identify the methylated-differentially expressed genes (MDEGs) that may serve as diagnostic markers and therapeutic targets in Epstein-Barr virus-associated gastric cancer (EBVaGC) and to explore the methylation-based pathways for elucidating biological mechanisms of EBVaGC. Materials & methods: Gene expression and methylation profiles were downloaded from GEO database. MDEGs were identified by GEO2R. Pathway enrichment analyses were conducted based on DAVID database. Hub genes were identified by Cytoscape, which were further verified by The Cancer Genome Atlas database. Results: A total of 367 hypermethylated, lowly expressed genes were enriched in specific patterns of cell differentiation. 31 hypomethylated, highly expressed genes demonstrated enrichment in regulation of immune system process. After validation using The Cancer Genome Atlas database, seven genes were confirmed to be significantly different hub genes in EBVaGC. Conclusion: EBVaGC-specific MDEGs and pathways can be served as potential biomarkers for precise diagnosis and treatment of EBVaGC and provide novel insights into the mechanisms involved.

翻译标题与摘要 下载文献
影响因子:3.89
发表时间:2020-01-28
DOI:10.1002/jcp.29562
作者列表:["Daryabari SS","Fathi M","Mahdavi M","Moaddab Y","Hosseinpour Feizi MA","Shokoohi B","Safaralizadeh R"]

METHODS:Gastric adenocarcinoma, like other cancers, is a multifactorial genetic disease, andmetastasis of cancer cells is one of the main features of this illness. The expressionlevels of the CFL1 gene have been modulated in this pathway. Using small interferingRNA (siRNA) in the treatment of gastric cancer is considered a hopeful genetherapeutic approach. The present study reported the level of CFL1 genes betweentumor and margin and healthy tissue of gastric cancer. Also, the features of a cationicnanoparticle with a polymer coating containing polyacrylic acid and polyethylenei-mine that were used in the delivery of CFL1 siRNA, were shown. Then thecytotoxicity, cellular uptake, and gene silencing efficiency of this nanoparticle wereevaluated with CFL1siRNA. Method:In this study, the CFL1 gene expression was measured in 40 gastricadenocarcinoma, marginal and 15 healthy biopsy samples by a real‐time polymerasechain reaction. Physicochemical characteristics, apoptosis, and inhibition of migrationof the delivery of CFL1 siRNA by nanoparticle and lipofectamine were investigated ingastric cancer cells. Result:The CFL1 expression was remarkably increased in gastric cancer tissues incomparison with the marginal samples and normal tissues (p< .05) and the biomarkerindex for CFL1 was obtained as 0.94, then this gene can be probably used as abiomarker for gastric cancer. After treatment of the AGS cell line by CFL1 siRNA, theCFL1 expression level of mRNA and migration in AGS cells were remarkablysuppressed after transfection. Furthermore, the amount of apoptosis increased(p< .05). Conclusion:Our results demonstrated that CFL1 downregulation in AGS cells caninterdict cell migration. Finally, our outcomes propose that CFL1 can function as anoncogenic gene in gastric cancer and would be considered as a potential purpose ofgene therapy for gastric cancer treatment

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